Chronic lymphocytic leukemia

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science.

This page was updated on May 26, 2022.

Chronic lymphocytic leukemia (CLL) is a typically slow-growing cancer that begins in lymphocytes in the bone marrow and extends into the blood. It can also spread to lymph nodes and organs such as the liver and spleen. Chronic lymphocytic leukemia develops when too many abnormal lymphocytes grow, crowding out normal blood cells and making it difficult for the body to fight infection.

The term "chronic" means that the disease develops slowly. The abnormal lymphocytes take longer to develop and multiply. A disease like CLL, therefore, may take several years before it becomes serious. Comparatively, the progression of acute lymphocytic leukemia (ALL) is very quick. ALL may advance in a much shorter period.

Different types of CLL

CLL may be slow-growing or fast-growing. Slow-growing CLL may not need immediate treatment, and with this type, patients may be able to live with the disease for many years without it causing any problems. CLL types that grow quickly may be more severe and require treatment right away. The care team determines whether CLL is slow- or fast-growing by removing a sample of leukemia cells during a biopsy and analyzing these cells in a laboratory.

CLL may also be categorized based on the type of cell it affects. There are two main types of lymphocytes: B-cells and T-cells. CLL may start in either of these cell types, but it usually affects B-cells (also called B lymphocytes). B-cell CLL makes up more than 95 percent of all CLL cases, according to the American Society of Clinical Oncology (ASCO). T-cell CLL is much rarer. Within each of these two main types, there are subtypes.

Possible causes of CLL

Like other types of cancer, CLL is caused by changes (mutations) within genetic material (DNA). Cancer-causing mutations tend to affect genes that regulate the growth and division of cells (oncogenes) or tumor suppressor genes, which are supposed to keep cell division in check and ensure that cells die when it’s time. CLL is thought to arise when lymphocytes begin to divide uncontrollably.

However, in most cases of CLL, it’s not known what prompts these mutations to arise. Scientists now know that people with CLL usually have a mutation in at least one of their 46 chromosomes. Certain changes in chromosomes 11, 13 and 17 have been linked to CLL. The way in which these changes bring about CLL isn’t well understood.

CLL-causing mutations generally are thought to arise randomly, over the course of one’s lifetime. CLL is rarely caused by mutations inherited from parents, but some inherited mutations may raise the risk of developing CLL.

Chronic lymphocytic leukemia symptoms

CLL is a slow-growing type of blood cancer, and many signs of CLL are vague. The symptoms of CLL tend to develop over time. For many people, CLL symptoms may at first seem to be some kind of non-specific change in overall health. There may be an increased sense of fatigue or weakness. Some people may experience flu-like symptoms, like night sweats or enlarged lymph nodes. Many people are diagnosed with CLL because of a blood test for an unrelated condition.

Potential CLL symptoms include:

  • Enlarged lymph nodes that may appear as a lump or swelling in the neck, underarm, abdomen or groin
  • Fatigue
  • Weakness
  • Pain or sense of fullness in the stomach
  • Fever
  • Infection
  • Night sweats
  • Unintentional and unexplained weight loss
  • Easy bruising or bleeding

Some of the conditions that may arise as CLL slowly develops and spreads may include:

  • Anemia: Red blood transports oxygen throughout the body. Low levels of red blood cells may reduce the blood’s overall oxygen carrying capacity. This condition can be evaluated by a complete blood count (CBC) test. Symptoms of anemia may include weakness, fatigue, lack of energy and shortness of breath.
  • Leukopenia: Lymphocytic leukemias affect the white blood cells responsible for producing antibodies and warding off disease. A decrease in the functional lymphocytes may diminish the body's immune system. Symptoms of leukopenia may include reduced immunity, more frequent infections and fevers.
  • Thrombocytopenia: Blood platelets are the particles in the blood that aid with clotting. A CBC test may reveal a low blood platelet count in patients who have CLL. Symptoms of thrombocytopenia may include easy bruising, bleeding or nose bleeds, and bleeding gums.
  • Swollen lymph nodes: In some cases, the leukemia may spread to the lymph nodes. The clusters of lymph nodes in the neck, armpits or groin may become noticeably swollen from the accumulation of excessive amounts of cancerous lymphocytes.
  • Enlarged liver or spleen: The excess lymphocytes may build up in the liver or spleen. An enlarged liver or spleen may cause a feeling of fullness after eating a small meal, loss of appetite or swelling in the abdomen.

Diagnostic tests

Some of the tests that may be used to diagnose CLL include:

  • Blood tests
    • Complete blood count (CBC): CLL is often discovered during routine blood tests because a common blood test, called a complete blood count (CBC), reveals the levels of different blood cells in the blood, which helps indicate CLL or another related condition. As a result, a CBC is often the first step in the diagnostic process. A high white blood cell count on a CBC suggests that the individual may have CLL or another leukemia or related disease. People with CLL also often have low red blood cell and platelet counts, which a CBC reveals.
    • Flow cytometry and cytochemistry: Cells collected during a blood test are sent to a laboratory, where they’re analyzed using methods called flow cytometry and cytochemistry. These tests reveal the specific type of leukemia cell present in the blood, differentiating CLL cells from other types of leukemia cells.
    • Genomic testing: The DNA of the cells may also be analyzed in the laboratory to discover whether they contain specific genetic mutations that indicate whether the cancer progresses quickly or slowly. Treatment options may depend on the genetic makeup of the cells and the mutations they carry.
  • Bone marrow aspiration and biopsy: This test involves removing a sample of bone marrow using a needle and then analyzing the cells within the sample in a laboratory. This procedure is generally not needed to diagnose CLL, as blood tests are good at discovering cancerous cells. However, some patients may have this test done before treatment to learn more about the cancer.
  • Imaging tests: Imaging tests, such as X-rays and computed tomography (CT) scans, use different techniques to generate images of the inside of the body. These scans are generally not needed to diagnose CLL but may be used to discover where the cancer has spread. Determining the extent of cancer spread is called staging. Staging comes after diagnosis and helps influence how the cancer is treated.

Risk factors for CLL

Some people may be more likely to develop CLL due to risk factors—anything that raises an individual's risk of getting CLL. Having one or several risk factors for CLL doesn’t mean that the patient will develop cancer, only that he or she is more likely to get it than people without these risk factors.

CLL risk factors include:

  • Having a family history of CLL: Close relatives of people with CLL (parents, siblings and children) are two to four times more likely to get the cancer.
  • Being older: CLL risk increases with age. It’s much more common in older adults. About 90 percent of those with CLL are older than 50, and 71 is the average age of CLL diagnosis, according to ASCO.
  • Being male: Men are slightly more likely to develop CLL than women due to unknown reasons.
  • Being of Russian or European descent: People whose ethnicity can be traced back to Russia or Europe tend to be more likely to get CLL. People from China, Japan and other Asian countries rarely develop CLL.
  • Having been exposed to certain chemicals: Some research suggests that people who were exposed to the herbicide Agent Orange, used during the Vietnam War, may have an increased risk of developing CLL. Long-term exposure to other pesticides has also been linked to CLL risk in some studies, but the association isn’t confirmed.

Chronic lymphocytic leukemia treatment options

CLL treatment may include radiation therapy, chemotherapy, stem cell transplant and/or immunotherapy. The patient's integrated team of leukemia experts will answer questions and recommend treatment options based on each patient's unique diagnosis and needs.

In some cases, patients won’t need immediate treatment, and will instead be monitored by their care teams. This is called “watchful waiting” or “active surveillance.” If the leukemia progresses, certain treatments may be recommended.

A common chemotherapy treatment for chronic lymphocytic leukemia is oral chemotherapy. Patients with CLL may receive FCR (fludarabine, cyclophosphamide and rituximab) and bendamustine.

External beam radiation therapy (EBRT) is a common radiation therapy option for CLL, and can help to reduce swelling in the lymph nodes, liver or spleen.

Each patient should work with his or her care team to develop a personalized chronic lymphocytic leukemia treatment plan. 

Next topic: What is chronic myeloid leukemia?

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